Cladribine After Natalizumab for Multiple Sclerosis

Recruiting at 1 trial location

Overseen By Rehana Hussain

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Texas Southwestern Medical Center

Must be taking: Natalizumab

Must not be taking: Corticosteroids, Cytokine treatments

Disqualifiers: PML, HIV, Hepatitis, TB, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to generate hypotheses regarding the safety, efficacy, and immunological impact of cladribine tablets after treatment with natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) and active secondary progressive multiple sclerosis (active SPMS).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have been on certain treatments like corticosteroids, cytokine treatments, or certain immunosuppressive therapies recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Cladribine for multiple sclerosis?

Research shows that Cladribine is effective in treating relapsing forms of multiple sclerosis, as it helps reduce disease activity and is well-tolerated by patients. Studies like the CLARITY and ONWARD trials have demonstrated its safety and effectiveness in managing symptoms and reducing relapses in patients with active multiple sclerosis. ^{1 2 3 4 5}

Is Cladribine safe for humans?

Cladribine has been studied for safety in people with multiple sclerosis, and these studies generally show it is safe for human use, though it is important to monitor for side effects during treatment. ^{1 2 4 6 7}

What makes the drug Cladribine unique for treating multiple sclerosis?

Cladribine is unique because it is an oral medication that allows for long treatment-free intervals after short-term use, unlike many other MS treatments that require frequent injections. It works by selectively reconstituting the immune system, which helps reduce relapse rates and slow disease progression. ^{2 4 5 8 9}

Research Team

Olaf Stuve, MD, PhD

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

This trial is for adults aged 18-60 with relapsing forms of Multiple Sclerosis, including RRMS and active SPMS, who have been on natalizumab therapy for at least a year. Participants must weigh over 40 kg, not be pregnant or breastfeeding, use contraception effectively, and have no recent MS relapses. Exclusions include HIV or hepatitis infection, TB history, immunocompromised status, certain prior treatments like myelosuppressives or live vaccines recently.

Inclusion Criteria

I am not pregnant or breastfeeding.

I have been diagnosed with a relapsing form of MS.

Willing to provide voluntary and informed consent based on the Health Insurance Portability and Accountability Act (HIPPA)

Exclusion Criteria

I am positive for HIV or hepatitis B/C.

I have been diagnosed with or suspected to have PML.

I have been treated with cladribine before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Washout

A washout period of 14 to 28 days after the last infusion of natalizumab before starting cladribine treatment

2-4 weeks

Treatment Year 1

Participants receive cladribine 10 mg tablets in two cycles during the first year

12 months

Multiple visits for administration and monitoring

Treatment Year 2

Participants receive cladribine 10 mg tablets in two cycles during the second year

12 months

Multiple visits for administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

6-12 months

Open-label Extension

Participants may opt into a 2-year extension study with no intervention, monitoring clinical and paraclinical disease activity

24 months

Treatment Details

Interventions

• Cladribine

Trial Overview The study tests the safety and effects of cladribine tablets in patients previously treated with natalizumab. It aims to understand how cladribine impacts the disease's progression and immune response in those with Multiple Sclerosis after switching from another treatment.

Participant Groups

Group I: Cladribine Experimental Treatment 1 Intervention

All study participants will receive treatment with cladribine 10 mg tablets at the recommended cumulative dose of 3.5 mg/kg, divided into 2 yearly treatment courses (1.75 mg/kg per treatment course). This regimen corresponds to the recommended dosage as per the USPI. Each treatment course is divided into 2 treatment cycles: * Administration of first treatment course (year 1 treatment): * First cycle: Starts on Day 1 of the study * Second cycle: Administered 23 to 27 days after the last dose of first cycle. * Administration of second treatment course (year 2 treatment): * First cycle: Administered at least 43 weeks after the last dose of year 1 treatment * Second cycle: Administered 23 to 27 days after the last dose of first cycle of year 2 treatment. The cycle dosage will be administered as 1 or 2 cladribine 10 mg tablets daily over 4 or 5 consecutive days.

Cladribine is already approved in United States, European Union for the following indications:

Approved in United States as Leustatin for:

• Hairy cell leukemia
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin's lymphoma
• Multiple sclerosis

Approved in European Union as Litak for:

• Hairy cell leukemia
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin's lymphoma

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

EMD Serono

Industry Sponsor

Trials

147

Recruited

27,800+

Dr. Shepard

EMD Serono

Chief Medical Officer since 2021

MD from University of Cincinnati Medical School, Fellowships in Hematology and Oncology at University of Chicago Hospitals and Clinics

Miguel Fernández Alcalde

EMD Serono

Chief Executive Officer

Bachelor's Degree in Pharmacy from the University Complutense in Madrid, MBA from the University of Alcalá de Henares, Master's Degree in Management from IESE Business School

Findings from Research

In a 96-week phase III study involving 1,326 patients with relapsing-remitting multiple sclerosis, cladribine tablets demonstrated a safety profile with a high treatment completion rate (88.6% for cladribine vs. 86.3% for placebo).

The most common adverse event was lymphopenia, which aligns with cladribine's mechanism of action, and while infections were more frequent in the cladribine group (48.3% vs. 42.5% for placebo), they were mostly mild-to-moderate, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study. Cook, S., Vermersch, P., Comi, G., et al.[2022]

Cladribine is an effective oral treatment for very active recurring multiple sclerosis, requiring only two short courses of administration over two years to maintain efficacy for up to four years, significantly reducing flare-ups and disability progression compared to placebo.

While cladribine is generally safe, it can cause lymphopenia and increase the risk of herpes zoster infections; however, long-term follow-up (up to eight years) indicates no greater risk of serious events like cancers or opportunistic infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Recommendations for the use of cladribine tablets in recurring multiple sclerosis]. Oreja-Guevara, C., García-Merino, JA., Saiz, A., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cladribine tablets added to IFN-β in active relapsing MS: The ONWARD study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Comparing switch to ocrelizumab, cladribine or natalizumab after fingolimod treatment cessation in multiple sclerosis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Cladribine in Multiple Sclerosis: Real-World Clinical Experience From 5 Tertiary Hospitals in Portugal. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Cladribine treatment for highly active multiple sclerosis: Real-world clinical outcomes for years 3 and 4. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

A prospective observational longitudinal study with a two-year follow-up of multiple sclerosis patients on Cladribine. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Cladribine: an investigational immunomodulatory agent for multiple sclerosis. [2013]

8. Germany pubmed.ncbi.nlm.nih.gov

[Cladribin. Development of an oral formulation for the treatment of multiple sclerosis]. [2021]

9. Spain pubmed.ncbi.nlm.nih.gov

[Recommendations for the use of cladribine tablets in recurring multiple sclerosis]. [2020]